title: Combinatorial roles for zebrafish retinoic acid receptors in the hindbrain, limbs and pharyngeal arches.
abstract: Retinoic acid (RA) signaling regulates multiple aspects of vertebrate embryonic development and tissue patterning, in part through the local availability of nuclear hormone receptors called retinoic acid receptors (RARs) and retinoid receptors (RXRs). RAR/RXR heterodimers transduce the RA signal, and loss-of-function studies in mice have demonstrated requirements for distinct receptor combinations at different stages of embryogenesis. However, the tissue-specific functions of each receptor and their individual contributions to RA signaling in vivo are only partially understood. Here we use morpholino oligonucleotides to deplete the four known zebrafish RARs (raraa, rarab, rarga, and rargb). We show that while all four are required for anterior-posterior patterning of rhombomeres in the hindbrain, there are unique requirements for rarga in the cranial mesoderm for hindbrain patterning, and rarab in lateral plate mesoderm for specification of the pectoral fins. In addition, the alpha subclass (raraa, rarab) is RA inducible, and of these only raraa expression is RA-dependent, suggesting that these receptors establish a region of particularly high RA signaling through positive-feedback. These studies reveal novel tissue-specific roles for RARs in controlling the competence and sensitivity of cells to respond to RA.
authors.affiliation: Department of Developmental and Cell Biology, Developmental Biology Center, University of California, Irvine, CA 92697, USA.
authors.forename: Angela
authors.initials: A
authors.lastname: Linville
authors.forename: Kelly
authors.initials: K
authors.lastname: Radtke
authors.forename: Joshua S
authors.initials: JS
authors.lastname: Waxman
authors.forename: Deborah
authors.initials: D
authors.lastname: Yelon
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Schilling
mesh_terms: D000825:Animal Structures / Q000166:cytology / Q000187:drug effects / Q000196:embryology / Q000378:metabolism; D000818:Animals; D019521:Body Patterning / Q000187:drug effects; D001934:Branchial Region / Q000166:cytology / Q000187:drug effects / Q000196:embryology / Q000378:metabolism*; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005121:Extremities / Q000196:embryology*; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D018398:Homeodomain Proteins / Q000378:metabolism; D008954:Models, Biological; D009928:Organ Specificity / Q000187:drug effects; D018168:Receptors, Retinoic Acid / Q000235:genetics / Q000378:metabolism*; D012249:Rhombencephalon / Q000166:cytology / Q000187:drug effects / Q000196:embryology / Q000378:metabolism*; D014212:Tretinoin / Q000494:pharmacology; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics / Q000378:metabolism*
chemical_list: D018398:Homeodomain Proteins; D018168:Receptors, Retinoic Acid; D014212:Tretinoin